The present invention relates to a new use of vitamin E.
Vitamin E is known as an antioxidant and protective vitamin for phospholipids of the cell membrane. Vitamin E maintains the permeability and stability of the cell membrane; cf. Lucy, Annals N.Y. Academy of Science 203, 4 (1972). There has further been known that vitamin E has a membrane-sealing effect; cf. F. Mittelbach and G. Bodechtel, Munchner Medizinische Wochenschrift 110 (1968) 36: 1988-1993. In erythrocytes, the simplest cells of the human body, there has been found that vitamin E provides a protective effect for the cell membrane. In tests with animals and humans, it has been proven that anemia is a first signal of a deficiency of vitamin E. The hemolysis of the erythrocytes will normalize upon administration of high doses of vitamin E; cf. William J. Darbey Vitamin Horm., 26 (50) pp. 685-704 (1968) and Phelps DL Pediatrics 63 (6) pp. 933-935 (1979). From these literature references, it is apparent that after the oral administration of from 200 to 800 mg of vitamin E over a period of from 1 to 4 days, the hemolysis of the erythrocytes is significantly improved as compared to patients suffering from vitamin E deficiency.
Vitamin E has further been used to treat sickle cell anemia over a period of from 6 to 35 weeks; cf. Natt CL. Am. J. Clin. 33, pp. 968-971 (1980); Natt CL. Am. J. Clin. Nutr. 32, pp. 1359-1362 (1979); Gawlik G. M., Fed. Proc. 35 (3), p. 252 (1976) and Gorash L. Bieri J. G. et al., Univ. Conn. Farmington, Conn.
It has further been known that a daily dose of 750 mg of vitamin E over a period of from 3 to 6 months was successfully used to treat thalassemia patients, whereupon a normalization of the hemolysis of the erythrocytes was observed; cf. Kahane I. ISR. J. Med. 12 (1), pp. 11-15 (1976).
Vitamin E has further been successfully applied to patients suffering from an acute hepatitis or an alcoholic hepatitis having a deficiency in vitamin E in serum; cf. Yoshiakawa T., Takemura S., Kato H. et al., Japan. J. Gastrovent, 74/7, pp. 732-739 (1977). Eventually, vitamin E has been used to treat patients suffering from anemia due to an iron deficiency, in which treatment it caused an improvement or normalization of the lipid metabolism in the bone marrow to occur in the course of from 4 to 8 weeks; cf. Takoshi Itaga, Central Clinical Laboratory Nagasaki University of Medicine, Japan.
More detailed investigations of the resorption of vitamin E have resulted in the finding that a large portion of the vitamin E is destroyed by the gastric acid so that only part of the vitamin E can display its effects in the body; cf. Arthur Vogelsang in Angiology 21, pp. 275-79 (1970).
From Arzneimittel-Forschung 24, No. 2 (1974) 202 and 21, No. 3 (1971) , there has been known that by means of vitamin E there results a substantial increase in tolerance of the heart-efficient glycosides, while a relation between the effect caused by vitamin E and the dose of vitamin E has been explicitly denied.
There has now been found that vitamin E surprisingly is suitable to enhance and improve the effects of coronary-active vasodilators and/or blood circulation promoters. These coronary-active agents, on the other hand, promote the activity of vitamin E.
This new range of indications was not foreseeable from the knowledge according to prior art and opens a new and wide field of applications of vitamin E.
The agents, whose activities can be improved according to the present invention, in the first place include the coronary-efficient nitro derivatives such as nitroglycerol (glycerol trinitrate), isosorbitol dinitrate, pentaerythritol tetranitrate and mononitrate compounds. These agents are used for the therapy and the prophylaxis of disturbances of coronary blood circulation and against coronary insufficiency and in the prophylaxis of angina pectoris.
It has been found that use of these active ingredients in combination with a sufficient dosage of vitamin E allows the duration of treatment to be substantially shortened. The symptoms of the diseases will be more rapidly reduced, so that after some time the applied dose of the nitro compound can be significantly lowered.
These results were not foreseeable and enable a therapy to be applied in which part of the chemically active compound is substituted by a substance of natural origin which, moreover, is present in every cell of the body.
Further agents whose effects can be enhanced according to the invention are agents promoting blood circulation such as Extract. Hippocastani and .beta.-hydroxyethylrutoside, on the one hand, and nicotinic acid and nicotinic acid ester or derivatives thereof, respectively, such as xanthinol nicotinate and inositol nicotinate, dihydroergotoxine methanesulfonate, dihydroergocristine methanesulfonate, and dihydroergocornine methanesulfonate, on the other hand. It has been found that upon application of said agents in combination with a sufficient dose of vitamin E, the symptoms in many patients will be faster reduced and after some months the amounts of the vasodilators and/or blood circulation promoters can be lowered.
Crucial for the efficacy of vitamin E to enhance and improve the effects of coronary-efficient and/or blood circulation-promoting agents, above all, is a sufficient dosage which should be at least 80 mg. Lower dosages of vitamin E are useless, since large parts are destroyed by the gastric acid and thereby lose their activity; cf. Arthur Vogelsang, in: Angiology 21, pp. 275-279 (1970).